Recent findings from epidemiological studies suggest that that there may be a link between the experience of early traumatic events and later development of psychotic symptoms. Animal studies provide a model of "stress sensitization" whereby early stressful events contribute to dopamine dysregulation and a sensitivity to psychosocial stress in young adulthood. "Prodrome" studies provide a unique opportunity to assess stress responsivity prospectively, prior to the onset of full psychosis, by identifying youth with an "ultra-high-risk" syndrome that confers approximately 35 percent risk for conversion to a full psychotic disorder within 2.5 years. In Study 1, we test the hypotheses that 1) UHR participants age 16-25 report a greater number of traumatic life events than healthy controls matched on age, gender and SES;and, 2) UHR participants show dysregulated stress-responsivity compared to healthy controls as exhibited by higher baseline salivary Cortisol levels, a slower return to baseline levels after a laboratory social stressor task, and higher Cortisol levels 16 hours after administration of dexamethasone, which triggers the negative feedback response of the hypothalamic- pituitary-adrenal axis. We will also collect pilot data to demonstrate the feasibility of a longitudinal follow-up to Study 1 by repeating clinical and stress-responsivity assessments with the UHR group 6- and 12-months later. We hypothesize that a greater number of traumatic events and dysregulated stress responsivity in the UHR group will predict later positive symptoms, poor functioning and risk for conversion to full psychosis. Identifying the mechanisms linking early trauma and later psychosis will allow us to identify potential targets for prevention and early intervention in psychosis, while future studies should examine possible gene- environment interactions between early trauma and candidate schizophrenia genes. PUBLIC HEALTH RELEVANCE: Schizophrenia is a chronic and debilitating disorder that affects approximately 1 percent of the population and costs society more than depression, dementia and medical illnesses across most of the lifespan. Examining the role of early adverse life events and stress-responsivity in young people at ultra-high-risk for psychosis will help to identify risk factors for the development of schizophrenia and potential targets for prevention and early intervention.